ペニシリン（その11）：４才化膿性髄膜炎の治療

４才男児の化膿性髄膜炎の治療経過について-------------------------

現在も子どもの化膿性髄膜炎にアミノベンジル・ペニシリンが使用されています。
その静脈投与量は肺炎に使用する５〜10倍量。ペニシリンは静脈投与では血液中
から髄腔への移行が悪い（脳脊髄関門があり）ためにペニシリンを高濃度にする
必要があります。この例ではペニシリンが１時間おきに静脈投与されています。
髄腔への直接投与は行なわれていない。後に成人の髄膜炎で有効とわかる。

４才の黄色ブドウ球菌による髄膜炎の治療に要したペニシリンの投与総量は
おおよそ6.8g（人への治験当時，ペニシリンの精製度は50〜70%ぐらいでその
化学組成，分子構造は不明）。この量を得る為には約6,800リッターの培養液が
必要で当時の回収率は１／３。少なくとも１０名の技術員が精製に従事しま
した。

不幸なことに子供は死亡。剖検（死後解剖）の結果は髄膜炎は治癒していたが，
脳動脈瘤の破裂で死亡。
-----------------------------------------------------------------------------------------------------
CASE 4. -----Boy, aged 4　1/2 years.

May 13, 1941. admitted with Cavernous-sinus thrombosis from septic spots on left
|||||||||||||||| eyelid and face following measles 5 weeks before. Had received 30g
||||||||||||||| sulphapyridine in 14 days before admission. Semi-comatose, incontinent of
|||||||||||||||| urine and feces. Gross oedema both eyelids(fig. 6a), especially Left, with
|||||||||||||||| bilateral proptosis. Complete bilateral external ophthalmoplegia and 2 dioptres
||||||||||||||| of papilloedema; neck rigidity; bilateral Kernig's sign and extensor plantar
||||||||||||||| response. Moist sounds both base.
||||||||||||||| Liver edge two finger-breadths below costal margin. Blood-culture sterile.
|||||||||||||| Lumber puncture gave a faintly yellow cloudy fluid under high pressure(see table III).
May 13: intravenous infusion of citrate saline at 10c.cm. an hour(rate maintained with
|||||||| slight variation for 9 days, the site of infusion being changed 4 times).
|||||||| Penicillin injected into infusion ; dose 100mg.hourly. for two doses,
|||||||| 50mg.hourly for four doses, then 25mg. hourly.
May 14: pus from incision made into left eyelid and swab from nose grew Staph. aureus.
|||||||| X rays:opacity of left antrum, ethmoids clear.
May 15: blood sample an hour after dose of penicillin showed no anti-bacterial activity;
|||||||| dose increased to 50mg. hourly. General improvement.
May 16: obviously better; swelling of eyelids largely subsided. Blood taken just before
|||||||| injection showed trace of antibacterial activity.
May 19: general and local condition vastly improved(see fig. 6b); bilateral 6th nerve palsy
|||||||| and extensor plantar response remained. penicillin reduced to 50mg. 3-hourly.
|||||||| Small corneal ulcer left eye treated with penicillin 1 in 5000, which caused no
||||||||  discomfort.
May 22: improvement maintained, patient talking and playing with toys.
|||||||| Chest clinically normal. Slight pyrexia still thought to be due to pyrogen in penicillin
|||||||| or to reaction from thromboses in veins used for injections(see fig.7). penicillin stopped.
May 26. progress good. Temperature normal. General condition excellent. eye movements
|||||||| returning. X ray of sinuses:only slight clouding left antrum; chest; patch of
 ||||||||consolidation
|||||||| left apex and small ring shadow right mid-zone. These thought to be embolic sighs but
|||||||| general condition so good that no further penicillin needed.
May 27: 1 A.M. vomited and had general convulsions. Lumber puncture gave uniformly
|||||||| blood -stained fluid under high pressure. Became comatose with neck rigidity,s
|||||||| positive Kernig' sigh and spastic limbs.
May 28: temperature began to rise again.
May 29: appearance much as on admission. penicillin 2g. given in next 36 hours,
|||||||| but died May 31.

TABLE III-----CEREBROSPINAL FLUID OF CASE 4
------------------------------------------------------------------------------------------
Date ------pressure ----Protein ----Red cells ----White cells------Culture
------------------------------------------------------------------------------------------
May13 ---Raised ------110 --------v. few ----------109 --------Staph.aureus
May14 ---Normal------100-------- v. few ----------372 --------Staph.aureus
May19--- Normal -------60-------- v. few---------- 110 --------Staph.aur. and alb.
May22--- Normal -------95-------- v. few -----------45 ---------Sterile
May27---- Raised #---- 120------ 14,600 -----------56 ---------Sterile
------ omission
-------------------------------------------------------------------------------------------
# Cell-count done after fluid had stood for several hours

Autopsy(Dr.A.H.T. Robb-Smith).-------- Brain showed no thrombosis of main venous
sinuses; adhesion and old hemorrhage in hypophysical region. Considerable old and
recent hemorrhage in region of pons and cerebellum due to rupture of aneurysm on
left vertebral artery. Cavernous-sinus region and left orbit occupied by oedematous
granulation tissue; left carotid arter partially occluded by thrombus in its cavernous
course and completely occluded in its bony course. Both lungs showed scattered
abscess cavities, larger ones being air-containing cysts lined by yellowish membrane;
smaller ones containing yellowish material not exactly resembling pus. other organs
not remarkable.

Histologically granulation tissue is essentially similar whether in lung abscess, orbital
tissues or covernous regions(fig.8). There is a small central area of necrosis sometimes
containing a few gram-positive cocci; around this is an oedematous exudate with lipoid
-containing histiocytes;surrounding this is a granulation tissue formed largely of histiocytes
containing lipoid and blood-pigment, lymphocytes and plasma cells with a very occasional
neutrophil leucocyte; this tissue is well vascularized and there is some fibroblastic
proliferation, greatest in periphery.

In the cavernous region some of the veins contain organising thrombus; the left carotid
and vertebral arteries show organising thrombi which do not appear to be infected,
but as there are large breaks in the media and elastica of the walls of both these vessles
it must be presumed that they are the late results of an acute arteritis probably of bacterial
origin. The other organs show no significant change.

The autopsy showed that the infection in the cavernous sinus, orbits and in the lung had
been almost entirely overcome, and that healing processes were well advanced.
Death was due to the ruptured mycotic aneurysm and not to a recrudescence of the
infection. Before this vascular accident the patient had been restored from a moribund
condition to apparent convalescence. No toxic effects from the penicillin were noticed.
------------------------------------------------------------------------------------------------------------

引用）Abraham EP, Chain E, Fletcher CM, Florey HW,Gardner AD, Heatley NG,
Jennings MA,: Further obsevations on Pniecillin. The Lancet, 238:177-188, August 16, 1941.

ご質問は--------
〒755ー0097
山口県　宇部市　常盤台１丁目20−2
上宇部こどもクリニック　萩原啓二　
電話： 0836-29-1155
Fax　: 0836-29-1156
E-mail: keijihagiwara@gmail.com